Millions of patients in the U.S. have been diagnosed with heart failure. Heart failure (HF) is not a specific disease, but rather a compilation of signs and symptoms, all of which are caused by an inability of the heart to appropriately increase cardiac output during exertion. HF may be caused by chronic hypertension, ischemia, tachyarrhythmias, infarct or idiopathic cardiomyopathy. The cardiac diseases associated with symptoms of congestive failure include dilated cardiomyopathy, restrictive/constrictive cardiomyopathy, and hypertrophic cardiomyopathy. The classical symptoms of the disease include shortness of breath, edema, and overwhelming fatigue. As the disease progresses, the lack of cardiac output may contribute to the failure of other body organs, leading to cardiogenic shock, arrhythmias, electromechanical dissociation, and death.
Delivering pacing during the refractory period is a type of non-excitatory stimulation (NES) that causes the release of catecholamines such as norepinephrine within the tissue of the heart. This chemical release results in an increased contractility of the cardiac tissue, which in turn, results in increased cardiac output, fewer symptoms of heart failure and improved exertional capacity.
The treatment of severe cardiac dysfunction and decompensated heart failure may include inotropic drug therapies such as the catecholamines dopamine and dobutamine or phosphodiesterase inhibitors milrinone or aminone. Although these agents may be beneficial in specific settings, they require administration of a drug, often by intravenous route, with systemic side effects and the time-consuming involvement of skilled clinicians. Electrical stimulation therapies are attractive alternatives because they may be administered by implanted or external devices very shortly after dysfunction appears or worsens and because their actions may be confined to the heart.
Delivering stimulation during the refractory period is a type of non-excitatory stimulation (NES) also denoted herein as refractory period stimulation (RPS) causes release of catecholamines such as norepinephrine within the tissue of the heart. This chemical release (modulated or regulated as described herein) results from selective electrical stimulation of innervated portions of the myocardial substrate. Because the electrical stimulation is delivered during the non-excitatory or refractory period wherein the discrete myocytes cannot contract, only the interstitial nerve fibers effectively receive stimulation. This results in increased contractility of the cardiac tissue which, in turn, results in increased pressure or flow, fewer symptoms of heart failure, and improved exertional capacity. NES neurostimulation employs one or more pulses applied shortly after a sensed depolarization or an initial pacing pulse is delivered and a resulting ventricular contraction occurs. These NES pulses are delivered during the refractory period of the cardiac tissue such that they do not result in another mechanical contraction or electrical depolarization.
Another type of electrical stimulation can be provided during the nonrefractory period of the cardiac cycle. This type of stimulation results in an additional electrical depolarization and, when appropriately timed, results in post extrasystolic potentiation (RPS). The additional depolarization, coming shortly after a first depolarization, is likely not associated with a sizable mechanical contraction. The contractility of subsequent cardiac cycles is increased as described in detail in commonly assigned U.S. Pat. No. 5,213,098. The mechanism is understood to depend on calcium cycling within the myocytes. The early extrasystole tries to initiate calcium release from the sarcoplasmic reticulum (SR) too early and as a result does not release much calcium. However, the SR continues to take up further calcium with the result that the subsequent cardiac cycle causes a large release of calcium from the SR and the myocyte contracts more vigorously. Excitatory RPS stimulation requires an extra electrical depolarization that is accompanied by a small mechanical contraction.
Another known treatment for HF patients involves using atrioventricular (AV) synchronous pacing systems, including DDD and DDDR pacing devices, cardiac resynchronization therapy (CRT) devices, and defibrillation systems, to treat certain patient groups suffering heart failure symptoms. These systems generally pace or sense in both the right atrium and right ventricle to synchronize contractions and contribute to ventricular filling. Cardiac resynchronization devices extend dual chamber pacing to biventricular pacing to achieve better filling and a more coordinated contraction of the left and right ventricles. These pacing therapies result in greater pulse pressure, increased dP/dt, and improved cardiac output. However, determining the appropriate pacing parameters is difficult. For example, optimizing the length of the AV delay requires obtaining pressure data involving an extensive patient work-up as set forth in commonly assigned U.S. Pat. No. 5,626,623. These pacing systems may also include atrial and ventricular defibrillators or other therapies for tachyarrhythmias. As a direct result of a tachycardia or as a sequela, cardiac function may deteriorate to the point of greatly reduced cardiac output and elevated diastolic pressure. Rapid termination of tachycardias prevents worsening of heart failure.
The above-described therapies, including pacing, CRT, NES, and defibrillation capability, may be used alone or in combination to treat cardiac dysfunction including HF. However, prior art systems have not achieved a comprehensive therapy regimen that coordinates these mechanisms in a manner that is both safe and effective. Delivery of electrical stimulation as the heart tissue is becoming non-refractory can trigger a tachyarrhythmia. This is particularly true if multiple high-amplitude pacing pulses are utilized. A second problem may be a shift in the magnitude of resulting potentiation or refractory interval due to the course of disease or medication. These may lead to unacceptable levels of potentiation performance, or loss of effect altogether. Therefore, readily obtaining the appropriate timing parameters associated with this type of therapy is essential.
What is needed is a system and method that combines the known therapies available for treating cardiac dysfunction including HF in a manner that optimizes mechanical function or cardiac output, while also minimizing any risks associated with possibly inducing an arrhythmia.
As discussed herein and in the related, incorporated-by-reference applications, an RSP therapy involves providing one or more pulses (e.g., one to a plurality of electrical pulses having programmable values, such as for instance 50 Hz pulse(s) with a pulse amplitude of 4-10 volts, nominal pulse width of 1 to 3 ms) during the refractory period of at least one ventricle. The pulses are delivered such that the ventricles do not experience a second depolarization following delivery of the pulse(s). The RPS therapy increases contractile function and stroke volume on subsequent contractions. The magnitude of the enhanced function is dependent on simulation timing, location, waveform characteristics, duration and frequency of RPS therapy delivery and the like. The delivery location can include multi-site locations within one or both ventricles (or via a coronary vein, a pericardial location, and/or single ventricular sites. The pulse or pulses can be bi-polar or uni-polar and the vectors of said pulse(s) can vary between any available electrodes.